Functional role of adrenomedullin (AM) and the gene-related product (PAMP) in human pathology and physiology

Abstract

The methods of the present invention demonstrate that adrenomedullin (AM) is expressed in human cancer cell lines of diverse origin and functions as a universal autocrine growth factor driving neoplastic proliferation. The present invention provides for AM peptides and AM antibodies useful in therapeutic, pharmacologic and physiologic compositions. The present invention additionally provides for methods of diagnosis, treatment and prevention of disease utilizing compositions comprising the AM peptides and antibodies of the present invention. The methods of the present invention also provide for experimental models for use in identifying the role of AM in pancreatic physiology. The methods pertaining to rat isolated islets have show that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was show by the methods of the present invention to increase insulin release fivefold, an effect that was reversed by the addition of synthetic AM.

1. A method of treating a cell proliferation disease or condition in a subject, the method comprising administering to the subject an effective amount of PO72 (SEQ ID NO: 3), thereby treating the cell proliferation disease or condition in the subject. 
     
     
       2. The method of  claim 1 , wherein the condition is related to aberrant fetoplacental growth. 
     
     
       3. A method of regulating neuronal activity in a subject, the method comprising administering to the subject an effective amount of PO72 (SEQ ID NO: 3), thereby regulating the neuronal activity in the subject. 
     
     
       4. The method of  claim 1 , wherein the disease is a tumor or cancer. 
     
     
       5. The method of  claim 4 , wherein the tumor or cancer cell is selected from the group consisting of adrenal, nervous system, lung, colon, ovarian, prostate, bone, pancreas, and breast.